Alpha-1-antitrypsin deficiency is a heritable disease entity which predisposes to premature emphysema and cirrhosis. The primary defect resides in the structure of the protein molecule and leads to its accumulation in the liver and sera deficiency. The site of synthesis is exclusively the liver. This research proposes to establish in vitro methods for the study of alpha-1-antitrypsin biosynthesis. This approach requires growth of differentiated liver cells and radioimmunologic techniques for the study of its synthesis. Both are under development. A second focus of the application is development of methods which will predict the fetal genetic status with respect to Pi type. If successful, prenatal diagnosis would be available for this inherited disease.